Based on the cellular analysis of experimental pancreatic carcinogenesis by azaserine and by 4-hydroxyaminoquinoline-1-oxide, we defined distinct types of preneoplastic lesions, atypical acinar cell nodules of the pancreas. The proposed study is aimed at characterizing the biological nature of these nodules, particularly with respect to the acquisition by such preneoplastic cells of the properties of resistance to the cytotoxic action of agents which induce selective acinar cell damage of the normal pancreas. The stimulation of cell proliferation is considered one of the important components of tumor promoters. By applying the specific measures of inducing sustained acinar cell regeneration in the pancreas of animals treated with carcinogens, we will test whether the development of pancreatic acinar cell carcinoma results from distinct stages, initiation and promotion. Thirdly, the comparative studies of the pancreatic acinar cells in vitro obtained either from the normal pancreas of from the azaserine-induced acinar cell carcinoma will be pursued. The study includes in vitro growth characteristics, tumorigenicity, functional capacity (enzyme synthesis and secretion), and the responses of cells to various hormones or pharmacological agents. The major goal of the proposal is to clarify the histomorphogenesis of pancreatic acinar cell carcinoma, and to gain further understanding of the biological behavior of preneoplastic and cancer cells.